Cost Analysis of Autologous Peripheral Stem Cell Transplantation Versus Autologous Bone Marrow Transplantation for Patients with Non Hodgkin's Lymphoma and Acute Lymphoblastic Leukaemia

We evaluated the costs of unpurged autologous stem cell transplantation in a non-randomised study of 54 consecutive patients with lymphoproliferative malignancies who have been transplanted at the Nijmegen University Hospital between July 1992 and March 1998. Thirty-five patients were transplanted with autologous peripheral stem cells (APSCT): 30 had non Hodgkin's lymphoma (NHL) and 5 acute lymphoblastic leukaemia (ALL). Nineteen patients were transplanted with autologous bone marrow stem cells (ABMT): 17 had NHL and 2 ALL. The number of progenitor cells (CFU-GM, BFU-E) and nucleated cells was significantly higher in peripheral blood transplants. The duration of cytopenia was shorter after APSCT. The leucocyte recovery to 0.5 × 10⁹ /L was 13 days for recipients of peripheral stem cells compared to 20 days for bone marrow recipients (P 4.001). The platelet recoveries to 20 × 10⁹L were 13 and 29 days, respectively (P = 0.001). This resulted in significantly shorter admission duration 24 days after APSCT versus 30 days (P = 0.003) after ABMT.

Furthermore, a statistically significant difference between both groups was observed for antimicrobial costs (mean: fl 2,939 vs fl 4,888; P = 0.008), platelet transfusions (median: 3 vs 7 units; P = 0.01) and erythrocyte transfusions (median: 6 vs 10 units; P = 0.03). The mean overall costs were lower in patients transplanted with stem cells from' peripheral blood: fl 34, 178 versus fl 43, 469 (P = 0.007). This study suggests that the APSCT results in significant cost savings due to shorter hospital stay and less costs of supportive care, despite higher mobilisation costs. The costs of blood transfusions and antimicrobials for patients with ALL were significantly higher when compared to patients with NHL.     

Impact of chemotherapy on the mobilisation, harvest and economic costs of autologous peripheral stem cell transplantation in patients with multiple myeloma

To evaluate factors affecting mobilisation and harvest and to calculate the economic costs of autologous stem cell transplantation in multiple myeloma (MM) we analysed 29 consecutive patients who had been transplanted at the Nijmegen University Hospital between January 1992 and February 1999. Thirteen patients had been treated with three or more melphalan cycles before transplantation (melphalan group), while four of the remaining 16 patients (no-melphalan group) had only received one melphalan cycle with an interval of one year or longer before harvest. The two groups were analysed for differences in mobilisation, harvest and the costs. Collection of a sufficient number of peripheral stem cells failed in 4 patients in the melphalan group, and these patients were transplanted with both bone marrow and peripheral stem cells. The greater need for growth factors (median 6,400 microg vs 4,500 microg) and the longer duration of admission (median 8 days vs 3 days) for mobilisation in the melphalan group increased significantly (p=0.01) the total mobilisation costs (median fl 13,876 vs fl 6,101). The greater number of apheresis sessions (median three) and the additional bone marrow harvests for patients who could not achieve a sufficient number of stem cells, increased significantly (p<0.001) the total harvest costs (median fl 9,690 vs fl 1,615) in the melphalan group. This resulted in significantly (p=0.008) higher overall costs of the procedure (median: fl 49,576 vs fl 35,889). The haematopoietic recovery of all groups was similar. The no-melphalan group was subdivided in two groups based on the median number of chemotherapy cycles before harvest. The heavily treated group had received more than 5 chemotherapy cycles and the moderately treated group four cycles or less. The median overall costs of these two groups were comparable (median fl 36,837 vs fl 34,351). This study suggests that the administration of stem cell toxic melphalan before harvest contributes to administration of more dosages of growth factor, longer admission duration for mobilisation and higher number of leukaphereses in order to collect sufficient number of stem cells. This resulted in significantly higher overall costs. More cycles of chemotherapy without melphalan did not increase significantly any studied parameter nor the total costs of procedure. Melphalan therapy or heavy pre-treatment did not prolong the repopulation interval, probably due to the infusion of similar number of progenitor cells.     

Cost analysis and quality of life assessment comparing patients undergoing autologous peripheral blood stem cell transplantation or autologous bone marrow transplantation for refractory or relapsed non-Hodgkin's lymphoma or Hodgkin's disease: a prospective randomised trial

The cost-effectiveness of autologous peripheral blood stem cell transplantation (PBSCT) compared with autologous bone marrow transplantation (ABMT) for refractory or relapsed non-Hodgkin's lymphoma (NHL) or Morbus Hodgkin (MH) was assessed. Costs were determined from the induction chemotherapy regimen up to 3 months after discharge from hospital following the transplantation. Quality of life was measured by the EuroQol, the Rotterdam Symptom Checklist (RSCL) and the SF-36. Patients were randomised according to a 2:1 ratio to undergo either PBSCT or ABMT. 62 patients underwent PBSCT and 29 ABMT. Costs of the transplantation period were significantly lower in the PBSCT group (15 008 Euros) than in the ABMT group (19 000 Euros). Significant differences in quality of life were all in favour of PBSCT and emerged using the RSCL, both on 14 days after the transplantation and three months after discharge. We conclude that PBSCT is associated with lower costs and a better quality of life than ABMT for patients with refractory or relapsed NHL or MH.     

A prospective study of autologous bone marrow or peripheral blood stem cell transplantation after intensive chemotherapy in myelodysplastic syndromes. Groupe Fran?ais des Myélodysplasies. Group Ouest-Est d'étude des Leucémies aigu?s myélo?des.

We prospectively assessed autologous stem cell transplantation for consolidation treatment in a trial of intensive chemotherapy in high risk myelodysplastic syndromes (MDS). In this trial, patients aged 55 years or less with no HLA-identical sibling and achieving CR were scheduled to receive unmanipulated autologous bone marrow transplantation (ABMT) preceded by a consolidation chemotherapy course. Forty-two of the 83 patients aged 55 years or less included in the trial (51%) achieved CR. Three were allografted in CR. Twenty-four of the remaining 39 patients who achieved CR (62%) received ABMT (16 patients) or autologous peripheral blood stem cell transplantation (APSCT) (eight patients). Indeed, as bone marrow harvest was often insufficient, APSCT was subsequently proposed after mobilization by consolidation chemotherapy followed by G-CSF. The conditioning regimen combined cyclophosphamide and busulfan. ABMT and APSCT were performed 1-7 months (median 3) after CR achievement. Hematological reconstitution occurred in all patients and tended to be faster after APSCT than ABMT although not significantly. Three patients died from the procedure, nine relapsed after 2-26 months and 12 (50%) were still in CR after 8-55 months. In autografted patients, median Kaplan-Meier disease-free survival and survival were 29 and 33 months from the autograft, respectively. Thus, ABMT or APSCT can be performed in almost two-thirds of MDS patients who achieve CR with intensive chemotherapy. PBSC collection may yield higher numbers of stem cells than marrow collection in some cases, and could improve the percentage of MDS patients autografted in CR. Longer follow-up is required to determine if autograft will prolong CR duration in at least some patients.     

Treatment of high-risk solid tumors of childhood with myeloablative chemotherapy and autologous stem cell transplantation

Sixteen consecutive stem cell transplantations (SCT) were performed after myeloablative chemotherapy in patients with high-risk solid tumors of childhood. Seven patients received autologous bone marrow transplantation (ABMT), seven received peripheral blood stem cell transplantation (PBSCT) and two received ABMT + PBSCT. The progression-free survival was similar in three types of transplants (57% ABMT, 43% PBSCT vs. 50% ABMT + PBSCT). The rate of relapse in site of distant organs was also similar (57% ABMT, 57% PBSCT vs. 50% ABMT + PBSCT). There was no statistically significant difference in the hematopoietic recovery time between each group. PBSCT group had a significantly fewer days of food intolerance and a lower morbidity than ABMT group. The disease-free survival was 71% for neuroblastoma, 50% for small round cell tumors and 25% for rhabdomyosarcoma. Post-SCT therapy for possible reinfused tumor cells should be mandatory to decrease the frequency of relapse.     

Comparison of marrow vs blood-derived stem cells for autografting in previously untreated multiple myeloma.

Sixty-three new untreated patients with multiple myeloma under the age of 70 years received C-VAMP induction treatment followed by high-dose intravenous melphalan (200 mg m(-2)) and autologous stem cell transplant, either with marrow [autologous bone marrow transplants (ABMT), n = 26] or with granulocyte colony-stimulating factor (G-CSF)-mobilized stem cells from the blood [peripheral blood stem cell transplants (PBSCT), n = 37]. This was a sequential study and the two groups were not significantly different for all known prognostic variables. The complete remission (CR) rate after high-dose treatment was the same for both groups [ABMT 84% and PBSCT 70%; P = not significant (NS)]. Neutrophil recovery to 0.5 x 10(9) l(-1) occurred at a median of 22 days in the ABMT patients compared with 19 days for the PBSCT patients (P = NS). Platelet recovery to 50 x 10(9) l(-1) was significantly faster in PBSCT patients (19 days vs 33 days; P = 0.0015), and the PBSCT patients spent fewer days in hospital (median 20 vs 27 days; P = 0.00001). There was no difference in the two groups with respect to starting interferon (58 days for ABMT vs 55 days for PBSCT), and tolerance to interferon was identical. The median overall survival (OS) and progression-free survival (PFS) for the PBSCT patients has not yet been reached. The OS in the ABMT patients at 3 years was 76.9% (95% CI 60-93%) compared with 85.3% (95% CI 72-99%) in the PBSCT patients (P = NS), and the PFS at 3 years in the ABMT patients was 53.8% (95% CI 34-73%) and in the PBSCT patients was 57.6% (95% CI 34-81%) (P = NS). The probability of relapse at 3 years was 42.3% in the ABMT arm compared with 40% in the PBSCT patients (P = NS). Thus, PBSCT patients had a faster engraftment and a shorter stay in hospital than ABMT; the survival outcome and probability of relapse was the same for both groups.     

自体造血干细胞移植联合大剂量放化疗治疗恶性淋巴瘤32例

目的观察自体造血干细胞移植(AHSCT)治疗恶性淋巴瘤的疗效.方法自1991年6月至2000年4月,用AHSCT治疗恶性淋巴瘤32例.其中非霍奇金淋巴瘤(NHL)23例,霍奇金病(HD)9例;行自体骨髓移植(ABMT)12例,自体外周血干细胞移植(APBSCT)20例.外周血干细胞动员方法均采用常规化疗(CE或CHOP)加细胞集落刺激因子(G-CSF或GM-CSF;或G-CSF+GMCSF)10μg*kg-1*d-1.预处理方案为BEAM方案和MEL140mg/m2(或+Vp-16200mg)+单次全身照射(TBI)8Gy.结果全部患者移植后均重建造血,随访至2000年5月30日,中位随访1020d.处于无病生存者24例(75.0%),1,2年无病生存分别为78.1%(25/32)和46.9%(15/32),最长存活8年.8例(25.0%)复发.全组患者无移植相关死亡.结论AHSCT联合大剂量放化疗对预后不良复发或敏感的恶性淋巴瘤疗效佳,优于常规化疗.APBSCT造血恢复比ABMT快.预处理方案中含TBI的放疗组与单用联合化疗组疗效差异无显著性,但含放疗组副作用大.     

Autologous transplantation for aggressive non-Hodgkin's lymphoma: results of a randomized trial evaluating graft source and minimal residual disease.

PURPOSE: To determine whether the source of autologous hematopoietic stem cells altered the clinical outcomes of patients undergoing high-dose chemotherapy and hematopoietic stem-cell transplantation (HSCT) for aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Of 105 high-risk, persistent, or relapsed NHL patients slated for an autologous HSCT entered onto this trial, 93 eligible patients were randomized to receive cytokine-naive autologous bone marrow transplantation (ABMT) (n = 46) or mobilized peripheral-blood stem-cell transplantation (PBSCT) (n = 47). All patients received carmustine, etoposide, cytarabine, and cyclophosphamide as the conditioning regimen. PBSCT patients also received identical mobilization with granulocyte colony-stimulating factor (G-CSF) 10 microg/kg/d, and both groups received G-CSF 5 microg/kg/d after the infusion of the stem-cell product until neutrophil engraftment. RESULTS: PBSCT patients had significantly faster engraftment of all cell lineages: median time to absolute neutrophil count > or = 500/microL, 10 days versus 13 days on the ABMT arm; median time to platelet count greater than 20,000/microL untransfused, 11 days versus 15 days on the ABMT arm; and median time to RBC transfusion independence, 8 days versus 16 days on the ABMT arm. The complete response rate was 72% for PBSCT and 54% for ABMT. The death rate before posttransplant day 100 was 2% on the ABMT arm and 6% on PBSCT arm. Event-free survival was 37% for PBSCT and 37% for ABMT. However, overall survival for PBSCT was 61% compared with 43% for ABMT. CONCLUSION: Patients with aggressive NHL receiving HSCT randomized to PBSCT demonstrated improved neutrophil engraftment and platelet and RBC transfusion independence. The complete response rate and EFS were not statistically different by randomization arm. Patients whose harvests were positive for minimal residual disease by molecular analysis had poorer EFS.     

Illness intrusiveness among survivors of autologous blood and marrow transplantation.

BACKGROUND: Illness-induced disruptions to lifestyles, activities, and interests (i.e., illness intrusiveness) compromise subjective well-being. The authors measured illness intrusiveness in autologous blood and bone marrow transplantation (ABMT) survivors and compared the results with survivors of solid organ transplants. METHODS: Forty-four of 64 consecutive ABMT survivors referred to the University of Toronto ABMT long-term follow-up clinic completed the Illness Intrusiveness Ratings Scale (IIRS), the Affect Balance Scale (ABS), the Atkinson Life Happiness Rating (ATKLH), the Beck Hopelessness Scale (BHS), and the Center for Epidemiologic Studies Depression (CES-D) Scale. Mean time from ABMT to evaluation was 4.6 +/- 2.8 years. All patients were in remission or had stable disease at the time of evaluation. Autologous blood and bone marrow transplantation patients' IIRS scores were compared with scores reported by recipients of kidney (n = 357), liver (n = 150), lung (n = 77), and heart (n = 60) transplants. RESULTS: Mean IIRS score for the 44 ABMT patients was 37.2 +/- 17 (maximum possible score, 91; minimum possible score, 13). Higher IIRS scores correlated with lower scores on the ABS (r = -0.54; P < 0.0001), and ATKLH (r = -0.44; P = 0.004), and with higher scores on the BHS (r = 0.58; P < 0.0001) and CES-D (r = 0.48; P < 0.0001). The authors compared IIRS scores from the ABMT survivors with scores from recipients of solid organ transplants. Scores were corrected for age, gender, and time from transplant to evaluation. Corrected mean IIRS scores for the marrow (37.5), kidney (38.9), heart (40.0), lung (30.1), and liver (32.3) transplant recipients differed significantly (P < 0.0001 by analysis of covariance). Higher scores among marrow, kidney, and heart transplant survivors were caused by increased scores in the instrumental domain of the IIRS that measures disruptions in health, work, financial situation, and active recreation. CONCLUSIONS: Despite achieving a remission after ABMT, patients continue to experience illness intrusiveness compromising subjective well-being.     

Infusion of a high number of CD34+ cells provides a rapid hematopoietic recovery and cost savings in autologous peripheral blood stem cell transplantation

BACKGROUND: The objectives of this study were to evaluate the effect of the number of infused CD34+ cells on hematopoietic recovery and on the cost in autologous peripheral blood stem cell transplantation (PBSCT). METHODS: Sixty-nine patients who received autologous PBSCT (ABSCT) were divided into three groups defined by the number of infused CD34+ cells. The number of days until 0.5 x 10(9)/l neutrophils and 50 x 10(9)/l platelets, the number of transfused blood products, the febrile days, the duration of parenteral antibiotics and the cost of additional supportive care (transfusions of blood products and parenteral antibiotics) were analyzed. RESULTS: Twenty-three patients received <2.5 x 10(6)/kg of CD34+ cells (group A), 25 patients received > or = 2.5 to 5 x 10(6)/kg of CD34+ cells (group B) and 21 patients received > or = 5 x 10(6)/kg of CD34+ cells (group C). Patients in group C had rapid neutrophil (p < 0.01) and platelet (p < 0.05) recovery and required less platelet transfusions (p < 0.05) than patients in other groups. Transfusions of red blood cell concentrates, the duration of febrile days or parenteral antibiotics were not statistically different between the two groups. The patients in group C required significantly lower costs for platelet concentrates and additional supportive care (p < 0.05). CONCLUSION: Infusion of > or = 5 x 10(6)/kg of CD34+ cells in ABSCT shortens hematopoietic recovery and reduces costs for additional supportive care.     

High-dose thio-TEPA with escalating doses of epirubicin and autologous hematopoietic stem cell transplant for refractory cancers]

We studied high-dose chemotherapy with autologous hematopoietic stem cell transplant for patients (pts) with non-Hodgkin's lymphoma (NHL) and breast cancer (BC) refractory to conventional therapies. The conditioning regimen consisted of thio-TEPA 6 mg/kg/day for 3 consecutive days with escalating doses of epirubicin (EPI) in dose steps of 120, 150, 180 and 210 mg/m2 on day 1. Mucositis was dose limiting toxicity at 210 mg/m2 on this regimen, and the recommended dose of EPI was judged to be 180 mg/m2. No cardiotoxicities were observed. There were 3 with complete responses (CR), one partial response (PR) in pts with NHL, 3CR and 5PR in pts with BC. The median duration of response was 8 months (mos) and 4 mos, respectively. Hematological recovery was significantly earlier in the pts receiving both autologous bone marrow transplant (ABMT) and peripheral blood stem cell transplant (PBSCT) than ABMT alone. This approach made it possible to overcome the prolonged PLT recovery, which was one of the major problems on ABMT.     

自体造血干细胞移植治疗中、高度恶性淋巴瘤

背景与目的:自体造血干细胞移植(autologoushemotopoieticstemcelltransplantation,ASCT)支持下的大剂量化疗目前已成为治疗对化疗敏感的淋巴瘤最有效的手段之一。本研究评价自体造血干细胞移植支持下的大剂量化疗加放疗治疗预后差的中、高度恶性淋巴瘤的疗效。方法:1995年11月～2001年5月收集到的13例病例中,非霍奇金淋巴瘤(non-Hodgkinslymphoma,NHL)11例,复发霍奇金淋巴瘤(Hodgkinsdisease,HD)2例。移植前首次完全缓解(firstcompleteremission,CR1)8例,第二次完全缓解(secondcompleteremission,CR2)4例,第二次部分缓解(secondpartialremission,PR2)1例。预处理方案:单纯化疗4例;化疗加受累区放疗6例;全身放疗加化疗3例。2例采用自体骨髓移植,11例行自体外周血干细胞移植。结果:本组病例回输单核细胞(mono-nuclearcell,MNC)和粒-巨细胞系祖细胞(granulocyte-macrophagecolony-formingcells,CFU-GM)的均数(范围)分别为2.55(2.07～3.31)×109/L和1.43(0.6～2.36)×109/L。随访到2001年10月,所有患者造血功能都获得重建。白细胞恢复到≥1.0×109/L和血小板>50×109/L的中位时间(范围)分别为6(7～35)天和8(6～32)天。CR持续时间为4～57个月,中位时间为16个月,1年生存率76.9%,3年生存率46.2%。结论:自体造     

造血干细胞移植治疗恶性血液疾病及实体瘤的研究

目的 :对 32例造血干细胞移植 (AHSCT)治疗恶性血液病和实体瘤的有关资料进行总结分析。方法 :ABMT组 16例 (NHL 7例 ,HL 6例 ,AML 2例 ,AL L 1例 ) ,13例采用 CBVA方案预处理 ,2例采用 HD- CTX TL I,1例采用 TBI HD- CTX预处理。APBSCT组 16例 (NHL 11例 ,HL 3例 ,MM1例 ,SCL C1例 )用 CTX G- CSF DXM方案动员 ,NHL 采用 CBV方案预处理 ,MM采用 CBM处理 ,SCL C采用 CEP方案处理。结果 :ABMT组 3年、5年生存率在 NHL组为 75 %、75 % ,HL组分别为 10 0 %、83.3 % ;APBSCT组 NHL的 2年、3年生存率为 80 .6 %、6 8.7% ,HL 的 2年、3年生存率均为 10 0 %。 1例 MM、2例 AML、1例 AL L 和 SCL C的存活期分别为 5年、19月、2年和 14月。移植相关死亡率为 0。结论 :造血干细胞移植是治疗恶性血液疾病及实体瘤 ,改善预后的主要手段之一。 ABMT组与 APBSCT组疗效相近 ,患者造血...     

Outcome in patients with myelodysplastic syndrome after autologous bone marrow transplantation for non-Hodgkin's lymphoma.

PURPOSE: The absolute risk of myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for non-Hodgkin's lymphoma (NHL) exceeds 5% in several reported series. We report the outcome of a large cohort of patients who developed MDS after ABMT for NHL. PATIENTS AND METHODS: Between December 1982 and December 1997, 552 patients underwent ABMT for NHL, with a uniform ablative regimen of cyclophosphamide and total body irradiation followed by reinfusion of obtained marrow purged with monoclonal antibodies. MDS was strictly defined, using the French-American-British classification system, as requiring bone marrow dysplasia in at least two cell lines, with associated unexplained persistent cytopenias. RESULTS: Forty-one patients developed MDS at a median of 47 months after ABMT. The incidence of MDS was 7.4%, and actuarial incidence at 10 years is 19.8%, without evidence of a plateau. Patients who developed MDS received significantly fewer numbers of cells reinfused per kilogram at ABMT (P =.0003). Karyotypes were performed on bone marrow samples of 33 patients, and 29 patients had either del(7) or complex abnormalities. The median survival from diagnosis of MDS was 9.4 months. The International Prognostic Scoring System for MDS failed to predict outcome in these patients. Thirteen patients underwent allogeneic BMT as treatment for MDS, and all have died of BMT-related complications (11 patients) or relapse (two patients), with a median survival of only 1.8 months. CONCLUSION: Long-term follow-up demonstrates a high incidence of MDS after ABMT for NHL. The prognosis for these patients is uniformly poor, and novel treatment strategies are needed for this fatal disorder.     

Increasing incidence of late second malignancies after conditioning with cyclophosphamide and total-body irradiation and autologous bone marrow transplantation for non-Hodgkin's lymphoma.

PURPOSE: Although the risk of myelodysplastic syndrome (MDS) has been well-described following autologous bone marrow transplantation (ABMT), the risk of solid tumors has been poorly characterized. We report the incidence and outcome of solid tumors at 10-year follow-up in a large cohort of uniformly treated patients who underwent ABMT for non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between 1982 and 1997, 605 patients underwent ABMT for B-cell NHL, with uniform conditioning with cyclophosphamide and total-body irradiation followed by reinfusion of autologous bone marrow purged with anti-B-cell monoclonal antibodies. Current information on relapse of disease and second malignancies was obtained via an institutional review board-approved questionnaire sent to the referring oncologists. RESULTS: Forty-two solid tumors, six non-MDS hematologic malignancies, 39 nonmelanoma skin cancers, and 68 cases of MDS/acute myelogenous leukemia (AML) were observed at a median follow-up of 9.5 years. A cumulative incidence model using death as a competing risk found that the 10-year incidence of second malignancy is 21%, with 10.0% non-MDS malignancies. The projected incidence of all malignancies at 15 years is 29%. The principal risk factor for second malignancy is increased age at ABMT (P = .0002). In the entire cohort, 9.6% of patients have died of second malignancy. CONCLUSION: Lengthy follow-up demonstrates a significant incidence of second malignancies after ABMT for NHL. Although the incidence of MDS/AML starts to plateau, the incidence of solid tumors continues to rise. Second malignancies are responsible for a significant fraction of overall mortality following ABMT.     

造血干细胞移植治疗中高度恶性非霍奇金淋巴瘤5例

造血干细胞移植治疗非霍奇淋巴瘤５例,包括４例第 完全缓中,高度恶性ＮＨＬ;１例高度恶性ＮＨＬ合并淋巴瘤白血病。其中自体骨髓移植４例,异基因外周血干细胞移植１例。所有病例的移植成功。４例ＡＢＭＴ患者已无病生存５０,４８,３９和３个月,１例ａｌｌｏ－ＰＢＳＣＴ发生慢性移植物抗宿主病,移植后１２人月死于白血病复发。结果显示ＡＢＭＴ是治疗中,高度恶性ＮＨＬ有效手段。     

Autologous bone marrow transplantation for Hodgkin's and non-Hodgkin's lymphoma

Modern high-dose therapy with autologous bone marrow transplantation (ABMT) used for the management of Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL) began about a decade ago. As more lymphoma patients are treated and followed for longer periods of time, the value of this procedure is becoming clearer. ABMT for low grade NHL has not been studied extensively and follow-up is too short to demonstrate definite efficacy, but initial reports have suggested advanced low-grade NHL might be eradicated for some patients. More than a third of patients with intermediate- and high-grade lymphomas that are refractory to standard therapy or demonstrate poor prognostic factors, when treated with high-dose therapy and ABMT, experience long-term, disease-free survival. About 30% of patients with Hodgkin's disease that was not eradicated with conventional therapy experience long-term, disease-free survival when treated with high-dose therapy and ABMT. Patients who cannot have ABMT because of some bone marrow abnormality, can be offered high-dose therapy and restoration of marrow function by transplantation of hematopoietic stem cells collected from the peripheral blood rather than the marrow with no increased risk of failure to achieve long-term, disease-free survival. Continued efforts to reduce the morbidity and mortality associated with high-dose therapy, to identify the optimal high-dose therapy for each histologic type of lymphoma, and to better identify those patients most likely to benefit will improve the value of high-dose therapy and ABMT.     

Lymphokine-activated killer function following autologous bone marrow transplantation for refractory hematological malignancies

Disease recurrence remains the major factor which limits the success of autologous bone marrow transplantation (ABMT) for refractory hematological malignancies. The administration of interleukin 2 (IL2) with or without ex vivo generated lymphokine-activated killer (LAK) cells represents a potential approach to eradicating residual disease after ABMT. However, since LAK precursor activity is radiosensitive, high dose chemoradiotherapy may abrogate LAK function and preclude clinical responsiveness to IL2 after ABMT. Furthermore, since lymphocyte subsets which mediate LAK activity may recover at different rates after ABMT, LAK cells may be phenotypically and/or functionally altered after ABMT. To determine whether IL2 responsive LAK precursor cells are present in the circulation after ABMT, peripheral blood mononuclear cells (PBMC) from 21 patients with acute leukemia or lymphoma were tested for IL2-inducible LAK activity 17-83 days after ABMT. Cells were cultured with IL2 (1000-2000 units/ml) for 4 or 5 days and then tested for cytolytic activity and/or cell phenotype. LAK activity against the Daudi cell line was detected in every PBMC sample from every patient at every time point tested. The Raji cell line and a fresh allogeneic ovarian carcinoma were also lysed by LAK cells generated after ABMT. In the subgroup of patients transplanted for non-Hodgkin's lymphoma, LAK precursor activity appeared comparable to that of healthy controls. Culture with IL2 resulted in increased mean IL2 receptor expression in lymphocytes from patients after ABMT (3.1-9.9%) and from healthy controls (3.1-12.0%). After culture with IL2, the percentage of cells bearing the natural killer cell-associated Leu-19 determinant was significantly higher in patient PBMC than in normal control PBMC (28.3 versus 8.7%). Positive and negative cell selection by fluorescence sorting after culture with IL2 revealed that most of the LAK activity after ABMT was mediated by the Leu-19+ cells. Although CD5+ T-cells were devoid of LAK activity, a subset LAK effectors was CD8+. Thus, LAK activity is rapidly reconstituted after ABMT and is mediated by cells phenotypically similar to those in normal controls. These results support the feasibility of IL2 +/- LAK as consolidative immunotherapy after ABMT.     

重组人粒细胞集落刺激因子促进自体造血干细胞移植后造血功能恢复的临床研究

背景与目的:高剂量化放疗联合自体造血干细胞移植(autologoushematopoieticstemcellstransplantation,AHSCT)能够提高某些实体瘤的疗效,该疗法的成功得益于重组人粒细胞集落刺激因子(recombinanthumangranulocytecolony-stimulatingfactor,rhG-CSF)的运用。本研究的目的是观察rhG-CSF对实体瘤患者自体造血干细胞移植后造血功能重建的影响。方法:将接受AHSCT的130例实体瘤患者分为rhG-CSF组和对照组,rhG-CSF组在造血干细胞回输后第6天开始连日给予rhG-CSF250～300μg/d,皮下注射,直至白细胞(whitebloodcell,WBC)≥5.0×109/L为止;对照组在造血干细胞回输后不给予rhG-CSF。结果:130例患者共完成移植132次,其中2例为2次移植。研究早期的24例患者采取自体骨髓移植,其中12例移植后给予rhG-CSF;此后的106例均采用自体外周血造血干细胞移植(2例为2次移植),其中47例移植后给予rhG-CSF。(1)rhG-CSF组和对照组自体骨髓移植患者住无菌病房的中位时间为33天和41天,WBC恢复到1.5×109/L以上的中位时间为14天和24天,两组之间的差异有显著性(P<0.05);两组血小板(platelet,PLT)恢复到20×109/L及50×109/L以上的中位时间均无显著性差异。(2)rhG-CSF组和对照组自体外周血干细胞移植患者住无菌病房的中位时间为17天和20天,     

Successful unrelated cord blood transplantation for relapse after autologous transplantation in non-Hodgkin's lymphoma

We report a 34-year-old male with relapsed non-Hodgkin's lymphoma (NHL) after autologous peripheral blood stem cell transplantation successfully treated with unrelated cord blood transplantation (CBT). The conditioning regimen included 12 Gy total body irradiation and cyclophosphamide. After the conditioning, a total of 3.14 x 10(7)/kg cord blood nucleated cells was infused on 14 February 2000. An absolute neutrophil count greater than 5 x 10(8)/l and a self-sustained platelet count greater than 50 x 10(9)/l were achieved on days 21 and 43, respectively. During the follow up period, grade I acute graft-versus-host disease (GVHD) and limited chronic GVHD occurred, but both were successfully treated with a dose modification of cyclosporine. After a follow-up period of 16 months, the patient is alive and free of disease. To our knowledge this is the first report of a successful unrelated CBT for an adult NHL patient who relapsed after autologous transplantation.